TAP1
Domain
The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2.
The nucleotide-binding domain (NBD) mediates ATP hydrolysis coupled to peptide translocation. Two ATP molecules are accommodated at distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD of one subunit, while the NBD from the second subunit completes the active site by contributing the C loop motif (LSGGQ). Each ATP molecule is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which is necessary for ATP hydrolysis.
Function
ABC transporter associated with antigen processing. In complex with TAP2 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules (PubMed:25377891, PubMed:25656091). Uses the chemical energy of ATP to export peptides against the concentration gradient (PubMed:25377891). During the transport cycle alternates between 'inward-facing' state with peptide binding site facing the cytosol to 'outward-facing' state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent 'outward-facing' conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the 'inward facing' state for a new cycle (PubMed:11274390, PubMed:25377891, PubMed:25656091). Typically transports intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome. Binds peptides with free N- and C-termini, the first three and the C-terminal residues being critical. Preferentially selects peptides having a highly hydrophobic residue at position 3 and hydrophobic or charged residues at the C-terminal anchor. Proline at position 2 has the most destabilizing effect (PubMed:11274390, PubMed:7500034, PubMed:9256420). As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation (PubMed:1538751, PubMed:25377891, PubMed:26611325).
Involvement in disease
MHC class I deficiency 1
MHC1D1
An autosomal recessive immunologic disorder characterized by chronic bacterial infections of the respiratory tract, beginning in the first or second decade of life and usually progressing to bronchiectasis. Patients have nasal polyps and may develop chronic necrotizing granulomatous lesions affecting the nasal cavity, upper respiratory tract, and skin.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.
Tissue Specificity
Highly expressed in professional APCs monocytes and dendritic cells as well as in lymphocyte subsets T cells, B cells and NK cells.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- The transmembrane segments seem to form a pore in the membrane.
Alternative names
ABCB2, PSF1, RING4, Y3, TAP1, Antigen peptide transporter 1, APT1, ATP-binding cassette sub-family B member 2, Peptide supply factor 1, Peptide transporter PSF1, Peptide transporter TAP1, Peptide transporter involved in antigen processing 1, Really interesting new gene 4 protein, PSF-1